The research in this application will accomplish three specific objectives and is concerned with the investigation of the glycoprotein hormones (follitropin (FSH), leutropin (LH), chronionic gonadotropin (hCG), and thyrotropin (TSH) and the lactogenic/somatotrophic hormones (prolactin, placental lactogen, and growth hormone). The first objective is to measure the thermodynamic parameters of the thermal denaturation of each hormone by means of differential scanning calorimetry, thereby gaining a better insight into the physical characteristics of each protein. The second objective is to use the two different series of homologous proteins as a tool to assess the sensitivity of differential scanning calorimetry to detect subtle and not-so-subtle differences in protein structure. The third objective is to study the temperature dependence of the binding of a hormone to its receptor by analysis of the binding data in a van't Hoff sense in order to define the binding process in thermodynamic terms. The long term objective of the thermal denaturation study is to be able to compare (chemically, enzymatically, or synthetically) modified analogues of the hormones to their native hormones in order to decide if the analogues may be of use in therapeutic instances. The extensive comparisons of calorimetric data from these two series of homologous proteins will result in a demonstration of the value of differential scanning calorimetry as an investigative tool for studying proteins of virtually any degree of relatedness. The long term objective of the thermodynamic analysis of the binding data is to be able to alter (or optimize) in vitro binding conditions to suit a particular need and to provide the basis for designing therapeutically useful analogues of the hormones which could advantageously compete for receptors in vivo. In addition to providing a major contribution to our understanding of the physical chemistry of protein and glycoprotein structure, this proposal also has a major emphasis on the endocrinology of the glycoprotein hormones and the lactogenic/somatotrophic hormones, on reproductive biology (especially in the male), and the endocrinology of the lactogenic process. The health related aspects of the proposal include an approach to a better understanding of the reproductive physiology of the male, lactogenesis in the female, and intervention in the endocrinological processes concerned with the interaction of a protein hormone with its receptor.